Abnormal immune mechanisms are being studied in patients with HBsAg negative chronic active hepatitis and primary biliary cirrhosis (PBC) selected according to strict diagnostic criteria. The in vitro cytotoxic capacity of lymphocytes and lymphocyte subpopulations (T, K and B cells) against a hepatic target cell and a non-hepatic target cell in tissue culture has been evaluated. T cell mediated help and suppression of pokeweed mitogen-induced immunoglobulin synthesis by B cells has been studied using radioimmunoassays to measure IgG and IgM synthesized by cultures of appropriate mixtures of lymphocyte subpopulations in vitro. The ability of T cells to proliferate when cultured with either autologous or allogeneic irradiated B cells (mixed lymphocyte reactions) has been assessed. Results of these studies include the demonstration in PBC of (1) reduced spontaneous cytotoxic function of a subpopulation of lymphocytes which lack surface immunoglobulin but bear Fc receptors; (2) diminished capacity of T cells to inhibit immunoglobulin synthesis in vitro; and (3) a deficiency of the autologous but not the allogeneic mixed lymphocyte reaction.